PROJECT SUMMARY/ABSTRACT Surgical resection for stage I-III lung cancer is the treatment of choice and provides the highest rate of survival. Although surgery offers a potential cure, postoperative complications such as pneumonia, dyspnea, and reduced physical functioning are common and contribute to medical costs, reduced quality of life, length of stay, 30-day readmission rate, cancer recurrence, and mortality. Improving preoperative pulmonary health and aerobic capacity improves postoperative morbidity and mortality. However, preoperative exercise studies require a longer period of time (4-6 weeks) than is clinically available to demonstrate an impact, making them non-feasible for patients awaiting lung resection surgery. These programs also require multiple supervised visits/week, rigorous exercise, posing a strain on the social support system not available for most patients. In other disease sites, a 2-4 week respiratory muscle training (RMT) program performed prior to bypass, abdominal and esophageal cancer surgeries reduces postoperative complications. In lung cancer, respiratory muscle weakness (diaphragm) is associated with reduced exercise capacity and survival as well as increased surgical complications up to two years post-thoracic surgery. Therefore, interventions targeting respiratory muscle function prior to lung resection represent a more practical solution to prevent postoperative complications. RMT will also increase the number of surgically eligible patients as well as expedite recovery, reducing risk of long- term consequences in this high-risk cohort. Our long-term goal is to have a better understanding of biomarkers that will predict postoperative complications and quality of life in lung cancer survivors. The overall objective of this application is to determine how a home-based program designed around strengthening the respiratory muscles will improve postoperative health. This project will also study mechanisms contributing to respiratory muscle dysfunction as well as examine the financial sustainability of a prehabilitation program. The central hypothesis is that preoperative respiratory muscle weakness contributes to negative postoperative complications and RMT will mitigate these effects. The following specific aims will be tested: 1) Assess the impact of a preoperative RMT program on respiratory muscle strength, postoperative outcomes and quality of life compared to a usual care group; 2) Determine the extent of diaphragm anabolic/catabolic pathway activation between the RMT and standard of care group; and 3) Determine the financial sustainability of a transitional home-based program. In our opinion, this program is innovative because it will deliver prehabilitation services to advance the cancer care continuum in a group of patient who may not have received services due to the shortened period. It will quantify the direct effects of RMT and lung cancer on diaphragm structure and function, thus developing new biomarkers to predict postoperative complications. Finally, it will maximize preoperative cardiorespiratory performance and postoperative outcomes in the brief 2-4-weeks prior to surgery. The proposed research is significant because it will advance the delivery of rehabilitation services for surgically eligible cancer patients.